Breaking News
February 16, 2019 - Therapeutic endoscopy has an expanding role in the treatment of IBD
February 16, 2019 - Catalyst Biosciences Presents Updated Data from Its Phase 2/3 Trial of Subcutaneous Marzeptacog Alfa (Activated) in Individuals with Hemophilia A or B with Inhibitors at the 12th Annual EAHAD Congress
February 16, 2019 - Rerouting nerves during amputation reduces phantom limb pain before it starts
February 16, 2019 - A Hormone Produced When We Exercise Might Help Fight Alzheimer’s
February 16, 2019 - Millions of British people breathe toxic air travelling to GPs
February 16, 2019 - Conformance of genetic characteristics found to be crucial for longer preservation of kidney graft
February 16, 2019 - Researchers use optogenetic tool to control, visualize receptor signals in neural cells
February 16, 2019 - New reversible antiplatelet therapy could reduce risk of blood clots, prevent cancer metastasis
February 16, 2019 - Testosterone is not the only hormone needed for penis development
February 16, 2019 - FDA Advisory Committee Recommends Approval of Spravato (esketamine) Nasal Spray for Adults with Treatment-Resistant Depression
February 15, 2019 - Heart surgery technology developed at Baptist Health debuts after years of secrecy
February 15, 2019 - Prescription Opioids Double Risk of Triggering Fatal Car Crash
February 15, 2019 - New study helps doctors better understand high blood pressure in pregnant women
February 15, 2019 - Beta wave control in Parkinson’s diseased brain could be a potential therapy
February 15, 2019 - Media representations of love may justify gender-based violence in young people
February 15, 2019 - Yoga May Help With Rheumatoid Arthritis Symptoms, Severity
February 15, 2019 - Obstructive sleep apnea linked to inflammation, organ dysfunction
February 15, 2019 - Master your mind: A challenge from WELL for Life
February 15, 2019 - Why Some Brain Tumors Respond to Immunotherapy
February 15, 2019 - Must-Reads Of The Week From Brianna Labuskes
February 15, 2019 - Researchers uncover novel mechanism and potential new therapeutic target for Alzheimer’s
February 15, 2019 - Genetic variations in a fourth gene associated with higher ALL risk in Hispanic children
February 15, 2019 - Disruptive behavioral problems in kindergarten linked with lower employment earnings in adulthood
February 15, 2019 - New bioengineered device enhances the production of T-cells
February 15, 2019 - HDL proteome behaves like a tiny Velcro ball that is rolling on surfaces
February 15, 2019 - Puerto Rican children more likely to have poor or decreasing use of asthma inhalers
February 15, 2019 - Quality of patient care does not improve after physician-hospital integration
February 15, 2019 - Synopsys release new software for implant design and patient-specific planning
February 15, 2019 - 6 out of 10 hip replacements last 25 years or longer
February 15, 2019 - Health Tip: What You Should Know About Antibiotics
February 15, 2019 - New research challenges medical consensus that adenoids and tonsils significantly shrink during teenage years
February 15, 2019 - Discovery of weakness in a rare cancer could be exploited with drugs
February 15, 2019 - UVA scientists find potential explanation for mysterious cell death in Alzheimer’s, Parkinson’s
February 15, 2019 - New rules requiring female athletes to lower testosterone levels are based on flawed data
February 15, 2019 - Researchers comprehensively sequence the human immune system
February 15, 2019 - Researchers study animal venoms to identify new medicines for treating diseases
February 15, 2019 - Movement of wrist bones revealed by MRI and computer modeling
February 15, 2019 - Philips introduces new premium digital X-ray room to help shorten patient wait times
February 15, 2019 - Women fare worse than men following aortic heart surgery, study finds
February 15, 2019 - High-protein and low-calorie diet helps older adults lose weight safely, shows study
February 15, 2019 - Drug microdosing effects may not measure up to big expectations
February 15, 2019 - Discharged, Dismissed: ERs Often Miss Chance To Set Overdose Survivors On ‘Better Path’
February 15, 2019 - A digitized lab environment to be showcased at smartLAB 2019
February 15, 2019 - Scientists uncover main mechanisms of fluconazole drug resistance
February 15, 2019 - New study seeks to understand how colibactin causes cancer
February 15, 2019 - Photoacoustic imaging accurately measures the temperature of deep tissues
February 15, 2019 - Large study finds no association between phthalate exposure and breast cancer risk
February 15, 2019 - New research explains presence of ‘natural’ magnetism in human cells
February 15, 2019 - Bio-Rad launches new digital PCR system and kit for monitoring treatment response in CML patients
February 15, 2019 - Excessive daytime sleepiness in OSA patients linked to greater risk for cardiovascular diseases
February 15, 2019 - Scientists shed light on damaging cell effects linked to aging
February 15, 2019 - Celiac disease may be caused by stomach bug in childhood
February 15, 2019 - NHS performance figures highlight the true scale of Emergency Department crisis
February 15, 2019 - High intensity exercise may improve health by increasing gut microbiota diversity
February 15, 2019 - Apellis’ APL-2 Receives Orphan Drug Designation from the FDA for the Treatment of Autoimmune Hemolytic Anemia
February 15, 2019 - Couples creating art or playing board games release ‘love hormone’
February 15, 2019 - Glimpsing The Future At Gargantuan Health Tech Showcase
February 15, 2019 - Common herbicide found to increase the risk of lymphoma
February 15, 2019 - Over-abundance of energy to cells could increase cancer risk
February 15, 2019 - Oxford Genetics appoints Jocelyne Bath as new Chief Operating Officer
February 15, 2019 - Castration-resistant metastatic prostate cancer responds to combination of immune checkpoint inhibitors
February 15, 2019 - Large-scale clinical trial begins to study liver transplantation between people with HIV
February 15, 2019 - Cannabis use among adolescents linked with increased risk of depression in adulthood
February 15, 2019 - Fractures, head injuries common in electric scooter accidents, UCLA study finds
February 15, 2019 - Prenatal maternal depression has important consequences for infant temperament, study shows
February 15, 2019 - Stereotactic body radiotherapy effective in treating men with low- or intermediate-risk prostate cancer
February 15, 2019 - Zogenix Submits New Drug Application to U.S. Food & Drug Administration for Fintepla for the Treatment of Dravet Syndrome
February 15, 2019 - Certain birthmarks warrant quick treatment, pediatricians say
February 15, 2019 - New machine learning method predicts if atypical ductal hyperplasia will turn cancerous
February 15, 2019 - Whole-genome sequencing and sharing real-time data could limit spread of foodborne bacteria
February 15, 2019 - FDA warns doctor for illegally marketing unapproved implantable device
February 15, 2019 - New injury documentation tool may provide better evidence for elder abuse cases
February 15, 2019 - Physiological age is a better predictor of survival than chronological age, shows study
February 15, 2019 - New study reveals high success rate for hip and knee replacements
February 15, 2019 - Prenatal exposures to BPA may pose threat to human ovarian function
February 15, 2019 - Suspicious spots on the lungs of children with rhabdomyosarcoma do not behave like metastases
February 15, 2019 - Diet drinks daily could raise stroke risk says study
February 15, 2019 - Many Systematic Reviews Do Not Fully Report Adverse Events
February 15, 2019 - Seven tips to protect your child from burns
February 15, 2019 - Keynote speakers announced for CBD Expo MIDWEST
Genetic variants reveal novel therapeutic targets for chronic kidney disease

Genetic variants reveal novel therapeutic targets for chronic kidney disease

image_pdfDownload PDFimage_print

The kidney does more than double or even triple duty compared to other organs – it extracts waste, balances body fluids, forms urine, regulates blood pressure, and secretes hormones. Given this complexity, when things go wrong, havoc can ensue, causing a suite of symptoms called chronic kidney disease (CKD), which includes toxin accumulation, fatigue, and high blood pressure.

By investigating how genetic variations drive the expression of genes within the filtering cells of the kidney, researchers have found new pathways to explain CKD development and could inform its treatment, according to a study led by Katalin Susztak, MD, PhD, a professor of Renal-Electrolyte and Hypertension and Genetics in the Perelman School of Medicine at the University of Pennsylvania. Susztak and team report their findings in Nature Medicine this week.

Earlier this year, Susztak’s lab generated an atlas for the kidney, which included a novel molecular definition of all cell types in the kidney. They concluded that each distinct type has a unique, non-redundant function and that specific dysfunction is associated with specific symptoms in people with CKD. From this, the team started on the path to understand how kidney disease develops at the level of a single cell.

“This study is the first to look at specific cell types and how their genetic variations can lead to disease development,” Susztak said.

CKD, a condition in which the kidneys are unable to clear waste, affects 700 million people globally. The overall prevalence of CKD in America is about 14 percent of the population, according to the National Institute of Diabetes and Digestive and Kidney Diseases.

The team created a database showing how genetic variation influences messenger RNA expression in kidney cells. By integrating information from CKD-related genome-wide association analysis (GWAS) with more specific approaches, researchers identified genes and cells associated with CKD. A GWAS gathers a set of variations in the order of DNA building blocks for certain genes in different individuals to see if any variant is associated with a disease or trait.

“In the past, many GWAS efforts have identified sequence variants for CKD, but the biological basis of these variants was poorly understood,” Susztak said. “We need to do more with all of the information we have sitting in GWAS databases to identify the genes, cells, and molecular pathways responsible for CKD.”

The team found that candidate genes thought to cause CKD–27 in all–were more abundantly expressed in the proximal tubule of the kidney as analyzed by single-cell RNA sequencing. Tubules are part of the fine filters of the kidney where nutrients are reabsorbed from the urine. From this list of 27 genes, they initially focused on one gene, the adaptor protein DAB2 in the TGF-β pathway and found that it was connected to many other genes central to proper kidney function.

Further experiments using two types of CKD mouse models confirmed that reducing DAB2 expression in tubules protected the mice from CKD. By lowering expression of the DAB2 gene, the cytokine TGF-β pathway did not induce fibrosis in a misguided wound healing reaction.

Moving this knowledge toward the clinic requires several more steps, Susztak said: “We are just starting to find which molecules have gone astray to cause disease in order to develop drugs to counteract overactive molecules that cause damage to healthy tissue.”

Source:

https://www.pennmedicine.org/news/news-releases/2018/october/genetic-variants-reveal-new-targets-for-chronic-kidney-disease-treatment

Tagged with:

About author

Related Articles